Articles and health studies about drugs, addiction and alcoholism, including the most recent scientific and medical findings.

Friday, October 12, 2007

Topamax for Alcoholism: A Closer Look

Epilepsy drug gains ground, draws fire as newest anti-craving pill

A drug for seizure disorders and migraines continues to show promise as an anti-craving drug for alcoholism, the third leading cause of death in America, the Journal of the American Medical Association (JAMA) reported in its current issue.

371 male and female alcoholics between the ages of 18 and 65 took part in the study. The subjects received either topiramate or a placebo. Over 14 weeks, patients taking topiramate showed a significantly higher rate of abstinence for 28 consecutive days or more. (Rates of abstinence increased slightly in the placebo group as well. Both groups received some psychological counseling.)

Topamax is currently only approved by the Food and Drug Administration (FDA) for use against seizures and migraine. The controversial practice of “off-label” prescribing—using a drug for indications that are not formally approved by the FDA—has become so common that Johnson & Johnson (JNJ) said it had no plans to seek formal approval for the use of Topamax as a medicine for addiction.

In an editorial accompanying the study, published in the October 10 issue of JAMA, Mark Willenbring of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) wrote: “We now have very high-quality evidence that shows efficacy. The medical world doesn’t wait for the indication. Topamax is a drug that many physicians have used and many patients have had an experience with because of its use in migraines.”

In addition, Topamax is already prescribed off-label in some cases for depression and Post Traumatic Stress Disorder, according to reports.

At present, there four medications legally available by prescription for alcoholism: disulfiram (Antabuse), SSRIs (off-label), naltrexone (Revia and Vivitrol), and acamprosate, the latest FDA-approved entry. Acamprosate binds to both GABA and glutamate receptors. Acamprosate, marketed in the U.S. as Campral, has been widely used in Europe on problem drinkers.

Dr. Bankole Johnson, chairman of Psychiatry and Neurobehavioral Sciences at the University of Virginia, told Bloomberg News that Topamax does everything researchers want to see in a pharmaceutical treatment for alcoholism: “First, it reduces your craving for alcohol; second, it reduces the amount of withdrawal symptoms you get when you start reducing alcohol; and third, it reduces the potential for you to relapse after you go down to a low level of drinking or zero drinking.”

According to Forbes.com, “The drug isn’t cheap—it costs about $1,000 for three months, according to Johnson. “And, patients, don’t see benefits for two to four weeks.”

Moreover, Topiramate is not without serious side effects for some users, including vision problems, difficulty remembering words, and a tingling in the arms and legs known as parasthesia.

The study was funded by Ortho-McNeil-Janssen, the subsidiary of Johnson & Johnson that produces and markets Topamax. Citing this and other alleged irregularities, Public Citizen’s Sidney Wolfe, Director of the Health Research Group, sent a stinging letter to the FDA demanding that the agency “stop the illegal and dangerous promotional campaign by Ortho-McNeil-Janssen-funded researchers for the unapproved use of Topamax (topiramate) for treating alcoholics.”

And to make things even more interesting, drug developer Mylan (MYL) received FDA approval last month for a generic form of Topamax, seeking a share of the estimated $50 million in annual sales the drug currently enjoys.

Like Campral, Topamax causes changes in the GABA and glutamate systems, which in turn affect dopamine and serotonin function. Acamprosate, like topiramate, harkens back to earlier work on GABA transmission in alcoholism. Both drugs attack the craving and relapse dilemma by stimulating GABA, the inhibitory transmitter that is the target of benzodiazepines like Valium, Xanax and Klonopin. However, Campral is not sedating. There is no buzz, no psychoactive effect, and no evidence of abuse potential whatsoever. Major side effects of acamprosate include gastrointestinal cramps and diarrhea. In addition, Campral may also “restore receptor tone” in the hyperactivated glutamate system of the alcoholic, specifically in the nucleus accumbens.

In a dozen clinical trials conducted in Europe, involving thousands of alcohol abusers, 50 per cent of acamprosate users maintained sobriety for three months without relapse, compared to 39 per cent of the placebo group. (The distressingly low numbers are testimony to the fierce mechanism of relapse.)

Topamax shows a similar mechanism of action. Earlier, researchers from the University of Texas conducted topiramate studies at the South Texas Addiction Research and Technology Center, later published in Lancet. Alcoholic patients achieved a rate of continuous abstinence six times higher than those in a placebo group did. They also reported fewer cravings, compared to a placebo group.

The downside to Topiramate may prove to be side effects. The NIAAA’s Raye Z. Litten, chief of treatment research, believes that the drug may ultimately be a strong player. “On the other hand,” he cautions, “Topiramate appears to have more severe side-effects than naltrexone and acamprosate.” Litten argues that greater efforts at testing are needed.

The National Institutes of Health (NIH) estimated that it would be sponsoring more than 30 new clinical trials of drugs for alcoholism in the next few years. The JAMA editorial, “Medications to Treat Alcohol Dependence,” concludes that the pace of development for alcoholism drugs in increasing. “A solid understanding of the neurobiology of alcohol addiction is providing the framework for multiple avenues of further medication development.”

35 comments:

Anonymous
said...

I think that alcohol abuse is like not having respect for your own body. And when you know that you're a heavy drinker and drive. Then you aren't only putting your life in danger ,but also the lifes of other inoccent people. You've written a great article that will inform and help a lot of people. Great job.

I have taken Topamax for about one year, following a increased dosage to 200mg. I had very mild early side effects, forgot a few words, but I can tell you, it is the only thing I have ever tried that worked, I no longer had the urge to drink the minute I went home. You might not believe in this drug, but it worked for me. I was off Topamax for about 6 months, and I started to slide again, but after using the drug again, it works for me.

I started taking Topamax 6 weeks ago for my migraines. Not only has it halved my migraine but it has completley stopped my alcohol cravings. Before taking this drug i didn't really know i had an alcohol problem but now i see i did - i was previoulsy drinking 2 -3 glasses of wine per day and couldn't wait to finish work to get home and have one and I feel fantastic that this craving has gone and I have not had a drink in 6 weeks!!

Regarding comment number one: Your comment is not useful in regard to this article. I.e. nobody cares what you "think" about alcohol abuse. This article is about a way to help people lessen the abuse of alcohol. I would direct you to the MADD website to post your opinions on alcohol abuse.

I agree with the Feb 2, 2009 comment. I never thought I'd be an alcoholic, and even know all of the reasons not to be, it can happen to anyone. Just be glad you aren't the one tring to deal with it. It shows no predjudice to race, education, sex, etc. I am just finally getting the nerve to start and my doctor said we might move to this after my initial month of other medications. This is encouraging.

I was just recently prescribed Topamax for alcohol/benzo addiction. Six weeks clean but terrible cravings. Anyways, my question is, I've been on it for a week now and I feel VERY tired and dizzy. Do these side effects lessen?

My medical doctor would not prescribe it either, I had to go to my psychiatrist. I also suffer from bi-polar, which topamax is also used for. My alcohol cravings ended for about a week then reared its' ugly head again. I am only on 50 mgs right now and am going to ask to up the dose to 100.

The very first poster obviously has no clue. Many people drink or use drugs as self-medication for depression, bipolar or other problems. They don't know their problems can be treated or they are ashamed to see a psychiatrist.

I have self-medicated with alcohol for bipolar for many years. Sometimes I'd quit and then start again. In 2008 after finding a new psychiatrist who put me on different meds, my bipolar was much improved, practically gone. I still drank as a bad habit. We tried Naltrexone and Campral with poor results.

Then we tried Topamax. It worked for me the very first day at only 50 mg. I lost the desire to drink completely. I took it for about a year and never had a drink. My meds allowed me to control stressful situations and I didn't even drink then. In the past I certainly would drink when stressed.

Occasionally I would forget a word but not more than many people do. Or maybe I just noticed it now.

I started Topamax about 18 months ago. Even after stopping I have no desire to drink 6 months later.

The article said Topamax is very expensive. Maybe it was without insurance, but a generic version is available now. Even an expensive drug will pay for itself if you can stop drinking.

And you don't have to go to AA to stop drinking. I have never attended a meeting.

i do not have insurance and now that there is generic topomax it costs me about $35 a month for my prescription. call around, especially the smaller, independentally owned pharmacies will work with you if they know you do not have insurance and are taking the med for bipolar or seizure or alcohol abuse.

To Ananymous who posted September 17th. Thank you for sharing your story. I am wondering if your dosage ever changed or if you stayed at 50 mg? I used Topomax for both migraines and alcohol control and it worked well. It is now several years later and I am calling my doctor tomorrow to get a script. The drinking came back for me, but I know the drug will help.

Topiramate did little to help me with my cravings or drinking over the year and a half I took it (50mg-125mg dosing).

The side-effects, though, were brutal. It's commonly called "stupomax" for a reason. As a creative writer, when on topiramate, I also found it extremely difficult to create anything. It didn't help much with my mood either (depakote/abilify/bupropion have been useful for this).

Also, don't take naltrexone if you enjoy music. It'll help with cravings, but numb out most other pleasurable experiences:

http://psycnet.apa.org/psycinfo/1981-12167-001

A. Goldstein, Thrills in response to music and other stimuli, Physiol Psychol 8 (1980), pp. 126–129.

kevincMy comment is each body/person is different...i experienced no loss of words nor musical sensation but i only took 20 mg a day..i couldn't tolerate Topamax very well it caused my blood sugar to go wacko and facial tremors... i would've kept upping the dose had it worked at all-it didn't work for me.

Topamax has been a godsend for me: bulimia, alcoholism, suicidal thoughts, anxiety, they all go away with this drug. I don't have weird tastes or issues with language. I think if it's the right drug for you, it just works. Sometimes it gives me some ringing in my ears, but I'll take that over the other stuff any day.

Just curious... of the people who have tried Topamax, do you consider yourself more of a Type 1 or a Type 2 alcoholic. I.e. Type one being later onset, no significant problems until 30's or 40's vs. Type 2 being early onset, heavy drinker from nearly the beginning accumulating significant consequences before midlife. On a scale of one to ten, with one being a Type 1 alcoholic and ten being a Type 2 alcoholic, how would you rate yourself. I myself am about an 8, but have not tried Topamax. Tried Campral, but had little success.

I have been on topamax 3 weeks now and it's been a miracle! I tried Naltrexone on the sinclair method for 9 months and then baclofen but couldn't tolerate higher than 100mg so had to quit. Topamax is working extremely well and did so from day 2!!! I reduced back down to 25mg again as I am currently confident it will continue to work. I will increase the dose to 50mg if I feel any craving again.

I've been on Topamax as a part of my Bipolar treatment for over a year now. I've been at a dose of 200mg for just about one year. The side effects did go away for me and weren't very bothersome in the first place. The tingling feet, the moments when I would forget a word. Ok, THAT was annoying, a "bipolar sister" and I sometimes dub this med "Dopamax". Haha.

Anyway, as I was reading about this study I was struck by something. I do occasionally have a couple beers here and there. Back before I was diagnosed, once I started drinking, I kept drinking. I know that I can't now, and that's part of why I stop. However, that inner push/want for another drink is no longer there. I don't even smoke weed anymore.

I come from a family full of addiction problems. I've had my own problems with alcohol and, though some feel it's not a "real" drug, smoking pit until every day was some fuzzy dream. We switched my medications a few times to find the right one to manage my manic episodes, and Topamax nailed it perfectly. Since last year, my pot/alcohol wants are gone. I thought I just got over it. Now, after reading a few articles about this, I'm starting to think this medication did even more good for me.

Side effects worry everyone. But if forgetting a few words and having tingling feet is it, I'd do it all again. They went away after a while, too. Before I was on Topamax, I was drinking while on my other meds (Lexapro, Lamictal, Abilify). That's NOT good! I was also the kind of person who wouldn't even take an Advil for anything. But this med is my miracle. And who knows what might have happened if I had kept drinking on my other medications. It just might have saved me.

I really hope they keep going forward with this study. I truly feel this may help many people.

Thank you to Anonymous who posted on July 31 of this year. I too come from a long line of addiction. I begin my Topamax regimen in two days, as it takes a few days to order where I live in Asia. My doctor had never heard of this treatment so he will be using me as a study. It will be interesting to see, absent a western situation, how this drug will affect me. I will be happy to keep posting as time goes on.

I don't know that it would work for off label use for addiction therapy but AstraZenaca has a program to give medication to those who need it. I was using Topamax off-label for compulsive cravings a few years ago and AZ issued me an insurance card to use at the pharmacy and the medication cost me nothing. If you think that this medication would be useful but not within your budget I suggest contacting the manufacturer as they were very easy to deal with and treated me great. Most drug companies have need based programs like this but the AZ program was was especially easy to get and helpful, everyone I dealt with at the company was great.

Did not find that Topirimate affected alcohol intake one way or the other. May have made hangover headache somewhat less intense. BUT--did cause considerable irritation--dryness--of eyes after several months of daily use.

What's with hassling the first poster? What.....drinkers can't take the truth?

NOTHING he said is inaccurate..Nothing. I guess any criticism is "hating" I guess.

DRINKING SHOWS NO RESPECT FOR YOUR BODY.I guess some pp on here think killing your liver,upping the chance of heart attacks, those loveless bags under your eyes, the wonders it does to your skin....and oh ya, all those glorious extra lbs of fat many drinkers carry around.....are GOOD THINGS, right?

DRINKING AND DRIVING IS A BAD THING.Really? Did I really read pp getting ticked at this guy for writing that?

I can't stop drinking......I know what it feels like....I seen my mind and body come down to crap because of it. I have No respect for myself AND those who beg my to quit. That's it. boozing is not something to br proud of....just like the guy said....i can't look in the mirror and bad mouth him, while I've thought the same things myself. And I'm not even gonna get into the drinking and driving thing.

I want to stop.....but it has gotten to be such a crutch......many pp have such bigger problems then I do and they handle it with strength and dignity....me, I hit the bottle........disease. Well it may be one now...but it wasn't for 45 years of my life..but, I allowed it to become one now.

I know everyone has a different set of circumstances...but I had to defend the opening poster..he may have hurt feelings, but he said nothing wrong.

I've been on this for about 5 months now. Started at 25 mg and now up to 175 increasing 25 mg about every 2 weeks. While I haven't stopped drinking my urges have subsided and I have at least stopped drinking liquor and am only drinking very cheap beer. Blood tests show my liver is now within normal ranges and tolerating the cheap beer that I'm drinking. Side effects occured when i first started - slight dizziness, slight weight loss, loss of appetite. Mental state seems fine, I manage about 60 people I dont think I'm doing any worse at work - in fact I feel like things are going a bit better. Good luck folks

I have been on Topamax for over 10 years mainly on 200 mg a day with minimal side effects. When I was first prescribed it was for miagraines and seemed to work well. It took me 3 months or longer to realize that it had also curbed my alcohol intake. Now while I had noticed the various side effects of appetite changes and verbal confusion, the alcohol wasn't apparent until pointed out to me. So, I thought you know what, lets see what happens if I try a drink. Nothing. Good or bad. Didn't get sick, Didn't feel great. Just like normal, but it started to change the body chemistry, and that caused problems. Then one drink turns into two, and two into five, and five into a fifth, and even now at 400mgs a day which can make me almost comatose I can still feel a craving for a drink. So the moral of the story is that if you start Topamax, and feel relief from the cravings...DON'T TEMPT FATE and DON'T TAKE ANOTHER DRINK

I had tried this drug in 2010 and didn't drink for about 8 mos. I had to stay with lower dosages due to side effects. I initially had dizziness and muscle weakness from the drug which made me worry. I slowly started drinking again after stopping the drug, then a bunch of stuff happened - death in the family, major illness, etc. and drinking is out of control again. I will probably go back to taking the drug - my hope is that side effects will bother me less. . .

It's not that alcoholics can't "handle" the truth, it's that what the first poster said isn't helpful. When someone is already in a shame spiral, shaming them further doesn't help. They're looking for answers, for a lifeline, for someone to tell them that there's hope, not someone to say "You're a drunk who doesn't care about yourself or other people." They already know that about themselves. Offer hope, not hate.

I have been fortunate to try this medication I noticed a significant reduction in craving and after 3 months went from drinking about 6 drinks every day to 3 per week. Then I quit the medication to see if I was ok and within 4 months I was back to 6 drinks every day I started again and am gradually getting back up to 100mg per day. I feel like it is starting to kick in again because I am actually not craving at all for 3 days now!If you do have a drinking problem I do advise to talk to someone for support and to try this medication it could save your life

I am now on Topamax for the second time. I'm up to 75 mg for bipolor 2 but it has also completely taken any alcohol desire away. Last April I started it as well but 2 months in started noticing I was losing extreme amounts of hair so stopped the medication. I was taking 125mg at that time and was also alcohol free, cravings, desires everything. After stopping the medication the cravings came back but the hair loss stopped. Any one else experience hair loss while on this medication? It has worked so well for me in completely dismising the alcohol desire hence I am willing to try it again.